News Update from the Sheba Multiple Sclerosis Center
The Multiple Sclerosis Center encompasses treatment facilities for 2000 patients with Multiple Sclerosis from all over Israel. We offer a Multi-Disciplinary Clinical Approach that integrates Patient-Care and Rehabilitation Activities. We are involved in basic Immunologic and Neuro-Molecular Genetic Research, and we also focus on development of Innovative Technologies associated with improved assessment of the Multiple Sclerosis disease process as well as patients quality of life.
Computerized MRI Analysis Unit
Multiple Sclerosis (MS) patients perform brain and spinal cord Magnetic Resonance Imaging (MRI) examinations as part of the diagnostic evaluation, and disease progression is assessed by follow-up MRI exams. We use the MS Analysis Computed program developed in our Center for quantitative volumetric measurement of the demyelinating lesions and for comparison of the change in MR lesion load overtime, to assess disease activity and treatment effects.
Clinical and Research
The Neuro-Immunology Laboratory is involved in the assessment of immune markers associated with the disease activity of MS, response to immunomodulatory treatments using short-term cultures, and pro-inflammatory cytokine production.
The Neuro-Molecular Gene Expression Laboratory is involved in gene expression studies using advanced microarray technology to define informative genes associated with disease activity and identify transcripts that can predict favorable response to drug treatments.
We conduct comprehensive and coordinated programs of rehabilitation related activities to assist achievements aimed to improve daily living, social integration, employment, and independent activities of disabled patients with MS.
T Cell Vaccination - T Cell Vaccination is a potential treatment for patients with Multiple Sclerosis. In the last two years, we have studied the safety and efficacy of T Cell Vaccination in patients with active disease who failed to respond to the conventional treatment modalities. The preparation of the vaccine was made by isolating the patient's own myelin-attacking T cells from peripheral blood, expanding the cells to auto-reactive lines, weakening them by irradiation and injecting them back to the patient. Three skin injections of the vaccine are given within six months and no side effects or significant adverse events were noted so far. The beneficial clinical results of the Vaccination Treatment prompted us to start an additional double-blind, placebo-controlled trial in Multiple Sclerosis patients with the first onset of neurologic symptomatology, in order to evaluate whether early T Cell Vaccination could induce long-lasting immunity against myelin-attacking cells and prevent the conversion from probable to definite Multiple Sclerosis.
Effect of Alphacalcidol (1-OH-Vitamin D) on MS-Associated Fatigue
Fatigue, occurring in 30%-80% of patients, is one of the most common symptoms of MS, and, for many, fatigue is the most disabling symptom. A randomized, double blind, placebo-controlled trial that includes150 patients with significant fatigue is currently evaluating the effect of Alpha-Calcidol on MS-associated fatigue. The possibility for an add-on drug that will affect fatigue in MS is of importance, as fatigue has a significant impact on activities of daily living, interfering with work, family life and social activities.
Antegren® Trial - The effect of the humanized antibody natalizumab (Antegren®) is being tested in an international multi-center clinical trial, as an add-on therapy for patients with Multiple Sclerosis already treated with Interferon-Beta 1-a (Avonex). Currently in our center, 20 patients have been enrolled to participate in this international study.
Our main research interests are aimed at innovative diagnostic procedures in the field of Immunology, visual processing, and analysis of MRI data and neurogenetics. Some of our major ongoing research projects include:
1. Prediction progression to disability - We developed longitudinal disability curves based on mean yearly measurements of neurological disability (measured by the Expanded Disability Status Scale -EDSS) and represented by percentile groups that enable plotting of disease progression over time. Using our computerized database that encompasses 1500 patients' records we identified subjects with a definite diagnosis of MS followed for up to 10 years. Construction of longitudinal disability curves and life-table analysis demonstrated that the probability of deviating from the initially assigned percentile is in the range of 6.5% (50th percentile) to 15.4% (75th percentile) and has significant predictive validity. We currently analyze the longitudinal disability curves to assess treatment effects and identify early non-responders.
2. Molecular portrait of Multiple Sclerosis using GeneChip expression analysis - Recent studies indicate that the tissue damage in MS occurs as the result of a pathological immune response to several myelin antigens after exposure to an environmental undefined causal agent(s) in subjects who are already genetically susceptible to the illness. The initial pathogenic process can be caused by one group of genes, while other groups could be responsible for the development and progression of the disease (Oksenberg, 2001; Compston, 1997). Using traditional methods of Molecular Biology it is hard to obtain a whole picture of related genes functions. To obtain insight into the pathological consequences of genetic modification in MS and better understanding of the effects of different treatment modalities, we initiated gene expression studies in different sub-populations of MS patients using microarray gene expression analysis.
3. Brain MRI lesion load quantification in Multiple Sclerosis - In order to establish a comprehensive basis for volumetric lesion load measurement of demyelinating lesions within the brain and evaluate correlations between clinical symptomatology and brain findings, we have developed a computerized automated technique to detect and segment MS lesions (Fig.2). The MS Analyze is based on advanced algorithms (e.g. Maxwell's optimization method, bayesian classification, near neighborhood) and enables the integration of data from at least three MR pulse sequences thus improving the thresholding power of the segmentation algorithm. We have recently completed validation studies assessing accuracy and reliability of the method. In ongoing experiments, we are examining the method in assessing treatment effects over-time and in correlation to clinical parameters and disease variables.
|Center at a Glance |
| Number of Patients per Year - 12000 + 2,000 visits in Day Care |
| Address - The Dolly Steindling Pavillion |
Director - Prof. Anat Achiron
Prof.. Anat Achiron is the Director of the Multiple Sclerosis Center. She completed her medical education at the Tel Aviv University Sackler School of Medicine, and received M.D. and PhD degrees. After her residency in Neurology she became interested mainly in clinical and basic research in Multiple Sclerosis and established the Multiple Sclerosis Center at the Chaim Sheba Medical Center, a center that has adopted a holistic approach in the treatment and rehabilitation goals for patients.
Her main research interests are related to the molecular, genetic, and immunologic aspects of the disease in relation to innovative therapeutic and diagnostic approaches, like T Cell Vaccination, Immunoglobulin Treatment and m-RNA expression profiles in different disease stages that can lead to the development of new drug targets and specific tailored treatment.
| E-mail - Anat.Achiron@sheba.health.gov.il|
| Tel - 972-3-530-3932 |